Prion hypothesis |
Castilla et al. (2005a) |
263 K |
Normal hamster brain homogenate |
PMCA-amplified PrPres induces bona fide prion disease in wild-type hamsters |
Deleault et al. (2007) |
Purified Sc237, purified 139H, or no seed |
Purified hamster PrPC with co-purified lipids, plus RNA cofactor |
Generation of infectious PrPSc from purified PrPC requires RNA cofactor in either seeded or non-seeded PMCA reactions |
Wang et al. (2010, 2015), Pan et al. (2020) |
No seed |
Bacterially expressed and purified recombinant mouse PrP, plus lipid and RNA cofactors |
De novo formation of infectious recombinant prion by PMCA requires lipid and RNA cofactors |
Prion strain |
Castilla et al. (2008b) |
5 murine prion strains, 4 human prion strains |
Normal mouse brain homogenate, brain homogenate from transgenic mice expressing human PrP |
PMCA-amplified prions faithfully recapitulate the strain-specific biochemical and biological properties of the seed prion strains |
Wang et al. (2010), Kim et al. (2010), Deleault et al. (2012b) |
No seed, mouse prion, or hamster prion |
Recombinant mouse or hamster PrP |
PMCA generated infectious recombinant prions manifest novel strain characteristics, which demonstrates the critical role of in vivo cofactors in maintaining strain properties |
Prion species barrier |
Castilla et al. (2008a) |
Mouse and hamster prions |
Normal mouse and hamster brain homogenates |
PMCA not only recapitulates the species barrier phenomenon in vitro, but also demonstrates its great potential to investigate strain adaptation and stabilization |
Green et al. (2008) |
Mouse prion |
Brain homogenate from transgenic mice expressing deer PrP |
PMCA-facilitated strain adaptation recapitulates the in vivo cross-species transmission that requires hundreds of days of adaptation and stabilization |
Pritzkow (2022) |
North American CWD and Norwegian CWD prions |
Normal mouse brain homogenate, brain homogenates from transgenic mice expressing PrP of various species |
Inter-species PMCA studies suggest North American and Norwegian CWD prions represent different strains with distinct cross-species conversion potentials |
Zoonotic potential of animal prion disease |
Jones et al. (2009) |
BSE, scrapie |
Brain homogenate from transgenic mice expressing human PrP |
First PMCA study to show the conversion susceptibility of human PrP to BSE but not scrapie prions |
Barria et al. (2011) |
CWD |
Brain homogenate from transgenic mice expressing human PrP |
CWD, after either in vivo passages in animals or in vitro passages by PMCA, is able to convert human PrPC to PrPSc, indicating the potential of CWD prions to infect humans |
Wang et al. (2021) |
CWD |
Non-CJD human brain homogenate |
CWD-seeded, PMCA-amplified human PrPSc is able to induce bona fide prion disease in humanized transgenic mice, demonstrating the ability of CWD prions to cross the species barrier and infect humans |
Pritzkow (2022) |
North American CWD and Norwegian CWD prions |
Brain homogenate from transgenic mice expressing human PrP |
Cross-species PMCA results indicate North American CWD prions have more zoonotic potential than Norwegian CWD prions |